Iranian Journal of Pharmaceutical Research
Volume:20 Issue: 1, Winter 2021

Onion (Allium cepa) is a member of the family Amaryllidaceae and one of the most widely cultivated species of the genus Allium. Onion has plentiful chemical compounds such as allicin, quercetin, fisetin, other sulphurous compounds: diallyl disulphide and diallyl trisulphide. Onion and its main components in specific doses have shown a lot of benefits including free-radical scavenging and antioxidant properties, anticholesterolemic, anti-heavy metals toxicity, antihyperuricemia, antimicrobial, anti-gastric ulcer, and anticancer. This study summarizes numerous in-vitro and animal studies on the protective effects of onion against natural and chemical toxicities.  Onion and its main components can ameliorate the toxicity of chemical agents in kidney, liver, brain, blood, heart, reproductive system, embryo, pancreas through reducing lipid peroxidation, antioxidant effect, radical-scavenging, anti-inflammatory, chelating agent, cytoprotective activities, increasing protein synthesis in damaged tissues, suppressing apoptosis, as well as modulation of PKC-𝜀/p38MAPK, Wnt/beta-Catenin, ERK, JNK, p38 MAPK, Bcl-2, Bax, and NF-κB signaling pathways.

The present study investigated the effects of co-administration of aspirin, metformin, atorvastatin and captopril on serum lipid profile and oxidative stress in the heart and kidney of streptozotocin-induced diabetic rats. In this study, rats were randomly divided into the following eleven groups: control (Cont.), and diabetic (D), as well as 9 groups that were treated with metformin (M, 300 mg/kg) or aspirin (ASA, 120 mg/kg) alone or in different combinations with captopril (C, 50 mg/kg), or atorvastatin (AT, 40 mg/kg), as follows: (D + M), (D + ASA), (D + M + ASA), (D + M + C), (D + M + AT), (D + M + C + ASA), (D + M + C + AT), (D + M + AT + ASA), and (D + M + C + AT + ASA). The rats in treatment groups daily received drugs by gavage for six weeks. Finally, serum lipid profile and levels of oxidative markers in the heart and kidney tissues were evaluated.In diabetic rats, blood levels of glucose, cholesterol, TG (triglyceride), LDL (low-density lipoprotein), MDA (malondialdehyde) and AIP (atherogenic index of plasma) significantly increased but those of HDL (high-density lipoprotein) and total thiol as well as SOD (superoxide dismutase) and CAT (catalase) activities significantly decreased. Treatment with different combinations of C, ASA, AT and M significantly ameliorated these parameters. This study showed that co-administration of ASA, M, C and AT, could improve glucose and lipid metabolism and oxidative stress markers in the kidneys and heart tissues of diabetic rats more markedly than the administration of these drugs alone.

Several studies have tried to find an efficient agent to prevent or reverse gentamicin (Gm) induced acute kidney injury (AKI). In this study, we assessed the potential renal protective effects of Descurainia sophia (L.) Webb ex Prantl against Gm-induced nephrotoxicity in rats. Thirty-five male Wistar rats were categorized in five groups (n = 7 per group). Control group was treated with normal saline. In four experimental groups, the rats were initially treated with normal saline (A), 800 (B), 1600 (C) and 2400 (D) mg/kg Descurainia sophia respectively for 28 days. After that, the rats of experimental groups were treated with Gm (80 mg/Kg) for 7 consecutive days. Blood and urine markers, as well as apoptosis and histological features were determined. Serum BUN, creatinine, cholesterol, and triglycerides level, as well as urinary excretion of Na+ significantly increased in group A. Furthermore, Gm induced inflammatory cells infiltration, apoptosis, and renal cells injuries in rats were pretreated with normal saline (group A). However, in the rats pretreated with Descurainia sophia extract (groups B, C, and D, there were significant and dose-dependent reductions in serum BUN, creatinine, cholesterol and triglyceride, urinary Na+ excretion, apoptosis rate, and inflammatory cells infiltration in renal tissues. Overall, Descurainia sophia showed significant protective effects against Gm-induced AKI by alleviating biochemical and histological markers of renal toxicity.

The Mashhad drug and poison information center (MDPIC) was officially established in 2000 to provide up-to-date information on medications. The objective of this study is to provide an epidemiologic profile of drug inquiry and poisoning-related phone calls to MDPIC from 2007 to 2017. This article is a descriptive retrospective study in which all inquiries about drugs and poisoning cases received by MDPIC, from 1st January 2007 to 31st December 2017, were retrieved from its database for analysis. A total of 100997 cases were analyzed. The most frequent calls were from individuals in the age group of 18 to 60 years old (70.21%). The majority of callers were women (73.08%). The public made 95.11% of calls, and 4.89% were related to health care professionals. The queries were mainly related to therapeutic uses of drugs (24.03%), followed by adverse drug reactions (18.96%). Given that 99.23% of calls were related to drug information inquiries, the most common drugs questioned about were antimicrobial (12.3%) and vitamin and minerals (10.76%), whereas 0.77% of calls were about poisoning and the majority of them were due to drugs poisoning. Micromedex® was the most commonly used reference to answer the inquiries. This report shows an updated epidemiological evaluation on recorded calls in the drug and poison information center in Mashhad. Since there is no other similar report, this can provide valuable information on the trend of drug usage and may guide further strategies in giving proper information to public and health centers.

There are conflicting data regarding the association between plasma concentration of voriconazole (VCZ) and both efficacy and safety. This study investigates the association of VCZ trough plasma level with clinical efficacy and hepatotoxicity in the Iranian population suffering hematological malignancies. This cross-sectional study was performed on adult Iranian patients (age ≥ 18 years) with hematological malignancies undergoing treatment with oral or intravenous VCZ for proven or probable invasive aspergillosis. Plasma concentrations of VCZ were measured at two time points on day 4 and 14 during the study period. A total of 60 VCZ trough concentrations of 30 patients were drawn on days 4 and 14 after the initiation of treatment. There was no definite correlation between the mean plasma concentration of VCZ and VCZ dosage (p = 0.134, r = 0.280). In multivariable model, only plasma concentration of VCZ on day 14 was associated with the incidence of hepatotoxicity (p = 0.013; OR = 1.42, 95% CI = 1.07-3.24). Plasma trough concentration neither on day 4 nor on day 14 was related to the treatment response. No significant association was observed between the mean plasma concentration of VCZ and 3-month patients’ survival (p = 0.696). To conclude, VCZ trough concentration may not be a predictor of treatment response or 3-month patients’ survival. However, the wide inter- and intra-patient variability of VCZ plasma concentration coupled with the observed association between VCZ trough level and the incidence of hepatotoxicity would pose the question regarding the potential benefit of VCZ concentration monitoring.

Molecular study of garlic as a popular food ingredient could better understand its health benefits such as immunological effects. For this aim, effects of garlic on the spleen and possible side effects including oxidative stress increment, the molecular mechanism is investigated through network analysis of differentially expressed genes in the treatment of garlic. Protein-protein interaction (PPI) network analysis of spleen gene expression profile of Mus musculus (8-week old male C57BL/6J mice) in garlic treatments from a microarray study with the code of GSE10344 was analyzed via GEO2R software. Furthermore, Cytoscape V 3.7.1 was applied to construct and analyze a network of up- and down-regulated genes. The differentially expressed genes (DEGs) were analyzed via the CluePedia plugin of Cytoscape to determine expression patterns. After the identification of central nodes, an action map was created. A total of 77 DEGs were achieved which were including 40 up-regulated and 37 Down-regulated. The centrality analysis of the network indicated that Vcan, Lamb1, and Ltbp1 are hubs and Glra1, Wdr17, Nefl, and Becn1 are bottlenecks. Mutual regulatory connections between hubs and Alb and App (as two non-queried hubs) were determined. The findings indicate that garlic effect on the spleen and its mechanism may be involved mostly with App dysregulation.

Antioxidant activity of five different extracts (petroleum ether, dichloromethane, ethyl acetate, ethanol and ethanol-water) of Artemisia aucheri aerial parts was investigated by three various methods ferrous ion chelating (FIC) assay, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging method and β-carotene bleaching (BCB) test. Total phenolic contents (TPC) were measured by Folin–Ciocalteu method. The hydroethanolic extract exhibited the stronger inhibitory activity in BCB and FIC assays than the other extracts. Among the extracts analyzed, the ethyl acetate and ethanolic extracts exhibited the highest TPC and DPPH radical scavenging activity, respectively. Reversed phase vacuum liquid chromatography of ethanolic extract (with the highest extraction yield) produced five fractions (A to E) which were subjected to all antecedent experiments. The same sample (Fraction C) showed the highest TPC and DPPH radical scavenging activity while there were no statistically significant correlations between TPC and EC50 values of various antioxidant assays. Ethyl caffeate and a spinacetin glycoside were isolated from the most active fraction and their structures were established using spectroscopic analysis including NMR and MS.

A new technique for cancer therapy is Photo Thermal Therapy (PTT). In the PTT technique, photon energy is converted into heat via various operations to destroy malignant tumors. Carbon nanotubes (CNTs) have good optical absorption in the near-infrared (NIR) spectrum and could transform optical energy into heat to induce hyperthermia in the PTT method. In this study, CNTs were firstly oxidized (O-CNT) and then decorated with silver nanoparticles (Ag NPs). Polyethylene glycol (PEG) was utilized for wrapping the surface of CNTs (O-CNT/Ag-PEG). Coating of CNTs with Ag NPs and PEG was confirmed by XRD, FESEM, and TEM techniques. Results demonstrated that noble metal could increase optical absorption of CNTs and concurrently improve the efficacy of the PTT technique. Cell cytotoxicity study showed that O-CNT/Ag NPs were less cytotoxic than O-CNTs, and O-CNT/Ag-PEG had the lowest toxicity against HeLa, HepG2, and PC3 human cell lines. The efficacy of O-CNT/Ag-PEG NPs in destroying malignant melanoma tumors was evaluated through the PTT technique. A continuous wave NIR laser diode (λ = 808 nm, P = 2 W, and I = 2 W/cm2) irradiated the tumor sites for 8 min once in the period of the treatment. The tumors in cases receiving O-CNT/Ag-PEG were shrunk efficiently compared to laser treatment ones. Results of in-vivo studies demonstrated that O-CNT/Ag-PEG was a puissant candidate in extirpating malignant tumors in PTT method.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Chemotherapy-induced adverse effects and resistance of NSCLC to conventional drugs reduce the efficacy of current therapies. Tumors contain a small population of cancer stem cells (CSCs) that play a critical role in tumor initiation, maintenance, and drug resistance that finally lead to cancer recurrence. Therefore, CSC-targeting therapies can offer the best hope for developing curative cancer therapies. Vitamins have a high potential for cancer prevention and treatment. Vitamins also ameliorate the side effects which occur in chemo-radio therapy. Menadione (2-methyl-1,4-naphthoquinone/vitamin-K3) is a synthetic form of vitamin K that indicated antitumor activities. The purpose of this study was to evaluate the anti-CSCs effect of menadione and combination of cisplatin and gemcitabine as a first-line treatment in patients with NSCLC on the NSCLC cell line A549. MTT results displayed decreased cell survival after treatment with cisplatin/gemcitabine for 48 h treatment (IC50 values 0.25 µM for cisplatin and 5 µM for gemcitabine). Menadione also inhibited the cell growth in A549 cells (IC50: 16 µM). Quantitative RT-PCR showed significant downregulation of CSC markers (Oct4, Nanog, Sox2, Aldh1, Abcb1, CD44, and CD133) and Snail, epithelial-mesenchymal transition marker, after treatment with menadione and cisplatin/gemcitabine. Flow cytometry showed CD44-positive cells that constitute a high percentage (70%) of A549 cells reduced significantly after treatment with cisplatin/gemcitabine or menadione. However, A549 cells did not show a significant population positive for CD133 and ABCB1 (less than 0.05%), and these fractions did not change after treatment with two agents.

Open innovation is a young arena in research that is fascinating the attention of a growing number of scholars. However, there are not enough studies that investigate open innovation performance. The pharmaceutical industry with the most Research and Development (R&D) intensity has been targeted by this new paradigm. This study explores the effect of entrepreneurial orientation on open innovation performance, considering the mediating role of desorptive capacity, which is defined as the firm’s capability to recognize outward technology transfer opportunities and to facilitate it. We use structural equation modeling to examine the hypotheses on a dataset from 100 Iranian pharmaceutical manufacturers in 2018. The results of the study support our conceptual model. Our findings indicate that a firm’s entrepreneurial orientation and desorptive capacity have a positive effect on its open innovation performance. Moreover, desorptive capacity has a mediating effect in the relation of entrepreneurial orientation and open innovation performance. This denotes that our new model contributes to the concept of desorptive capacity in the context of open innovation.

Epigenetic mechanisms are the most important factors contributing to both the development and metastasis of cancer cells. We aimed to scrutinize the role of epigenetic alternations of genes involved in cancer metastasis, including CD44v6 (metastasis indicator) and Nm23-H1 (a novel tumor suppressor), in the A549 lung cancer cell line. The A549 cells were cultured in the DMEM medium. Valproic acid (VPA) was used as a histone deacetylase inhibitor. Caspase-3 activity was assessed by adding DEVD-pNA substrate to the cell lysate. Gene expression was determined by real-time PCR. Finally, protein expression was assessed by western blot. The results showed that VA significantly decreased the expression of the CD44v6 gene and its protein level. This was further accompanied by lower expressions of MMP-2 and MMP-9 genes. On the other hand, the expression of Nm23-H1 and its protein were significantly increased in the cells accompanied by higher activity of caspase-3 (P ˂ 0.05). Our results showed that epigenetic regulation of CD44v6, Nm23-H1, MMP-2, and MMP-9 might be involved in the pathogenesis and metastasis of lung cancer. Therefore, the use of histone deacetylase inhibitors can be effective in the suppression of metastases and the treatment of these tumors.

The human epidermal growth factor receptor (HER) family plays pivotal roles in physiologic and pathologic conditions (such as tumor growth, proliferation, and progression in multiple epithelial malignancies). All the family members are considered tyrosine kinase, while HER3 as a member of this family shows no intrinsic tyrosine kinase. HER3 is called ‘pseudokinase’ because it undergoes heterodimerization and forms dimers such as HER2-HER3 and HER1 (EGFR)-HER3. The exact role of HER3 in cancer is still unclear; however, the overexpression of this receptor is involved in the poor prognosis of malignancies. To that end, different studies investigated the development of radiotracers for imaging of HER3. The main focus of this review is to gather all the studies on developing new radiotracers for imaging of HER3.

The effects of morphine on serum reproductive hormone levels and markers involved in fertility-relatedpathways were evaluated. A total of 30 male Wistar rats were divided into three groups (n = 10) and intraperitoneally administered the following substances for 20 days: two single daily doses of morphine (10 mg/kg; morphine group), saline (healthy saline), and intact group. After confirming the morphine dependence of the experimental groups, all the animals were sacrificed and their total testis tissue was extracted and stored at −80 °C until use. Male reproductive parameters (blood serum of testosterone, luteinizing hormone, and follicle-stimulating hormone) and using Q-PCR and western blot, we evaluated mRNA and protein expression of CREM, TBp , CREB1, HDAC1, and FOS involved in fertility-related pathways were analyzed and compared in the testis samples. The luteinizing hormone and testosterone levels were significantly lower in the morphine-administered group than in the saline and intact groups (P < 0.05). Moreover, the expressions of all five target genes were downregulated in the morphine group (P < 0.05). The protein expression of all five target proteins was downregulated in the morphine group (P < 0.05). We concluded that morphine could decrease the reproductive parameters in male rats.

In the current study, a liquid chromatography coupled mass detector was set up to detect and quantify 108 pesticide residues in rice samples. QuEChERS method was applied for sample preparation and different validation parameters were determined to ensure the suitability of the method. The calibration curves were linear in the concentration 0.01-1.00 mg/kg with a coefficient of determination (R2) of more than 0.990 for all compounds. Based on signal to noise studies, the calculated LODs and LOQs were 0.005-0.060 mg/kg and 0.018-0.199 mg/kg, respectively; and acquired mean recoveries at three spiked levels (0.025, 0.200 and 0.800 mg/kg) were 72% - 117% with RSD < 20%. The developed method was used to investigate the occurrence of the studied pesticides in 65 internal and 65 foreign rice samples. The results showed that 14 internal and 15 imported samples were found to be contaminated 12 pesticides in the amounts between 0.027 mg/kg to 0.078 mg/kg and 0.031 mg/kg to 0.081 mg/kg, respectively. According to the Iranian regulations, with the exception of nine prohibited pesticides for rice production in Iran, bioallethrin, cypermethrin, deltamethrin, flutriafol, foramsulfuron, imazalil, phosphamidon, TCMTB, and triasulfuron, three permitted pesticides, cinosulfuron, triadimenol, and tricyclazole, found in positive rice samples were below MRLs established by Iranian National Standard Organization (INSO).

The historical approaches that have been used to establish cleaning validation acceptance limits should be updated to recent approaches to prevent cross contamination. In the present investigation, a cleaning method was validated using high performance liquid chromatography. Method modification critical parameters including spiking, swab sampling from PVC, Stainless Steel, and Polyethylene, extraction technique from swab, solubility, potency, toxicity (LD50), and improvement of limit of detection (LOD) of the method through analytical method validation were studied. In addition, roughness, mechanical and electro-polishing, consideration of dosage form as a quantitative factor, acceptable daily exposure (ADE), and permitted daily exposure (PDE) in the worst-case determination were considered in the study. The method was validated based on USP and ICH guidelines for specificity, limit of detection, limit of quantitation, precision, accuracy, linearity, and range. Linear regression analysis of data for the calibration plot in the range of 7.43, 10.89, 21.78, 43.56, 87.12 μg/mL, and relative standard deviation (R.S.D.) found to be 0.5, 0.4, 0.2, and 0.2, respectively with correlation coefficient of R2 = 0.999997. The LOD and the limit of quantitation (LOQ) were 2.23 and 7.43 μg/mL, respectively. Good recoveries in the range of 73.65-81.20%, and precision with relative standard deviation values lower than 15% have been obtained. The proposed method developed for cleaning validation is specific, precise, and useful for determination of cleaning acceptance limits using health-based limit and Quality Risk Management to develop an appropriate cleaning program for engineering design, safety of patients, and worker protection.

Elastic or deformable liposomes are phospholipid-based vesicular drug delivery systems that help improve the delivery of therapeutic agents through the intact skin membrane due to their deformable characteristics that overcome the problems of conventional liposomes. In the present review, different types of deformable liposomes such as transfersomes, ethosomes, menthosomes, invasomes and transethosome are studied, and their mechanism of action, characterization, preparation methods, and applications in pharmaceutical technology through topical, transdermal, nasal and oral routes for effective drug delivery are compared for their potential transdermal delivery of poorly permeable drugs. Due to the deformable characteristics of these vehicles, it resulted in modulation of increased drug encapsulation efficiency, permeation and penetration of the drug into or through the skin membrane and are found to be more effective than conventional drug delivery systems. So deformable liposomes can, therefore, be considered as a promising way of delivering the drugs transdermally.

Benign prostatic hyperplasia is a common chronic disease that is age-dependent. There are two main types of interventional treatment, transurethral resection of prostate as a gold standard (TURP) and open prostatectomy (OP); also, there are two pharmacological groups for managing BPH: alpha-blockers and 5-alpha-reductase inhibitors (5-ARIs). In this economic evaluation study, one 5-ARIs, dutasteride and two main surgical treatments are compared as alternatives for treating moderate BPH in Iran. A cost-utility study with an Iranian health provider perspective was conducted. Markov model in a cohort of 1000 patients with BPH with annual cycle length and ten years’ time horizon was developed by using MS EXCEL 2013. The effectiveness measure was an improvement in the IPSS score and transformed to the utility. The transition probabilities, utilities and adverse events were extracted from published clinical trials. The direct medical costs were measured in the 2017 US Dollar. One way sensitivity analysis and scenario analysis were conducted.For treating moderate BPH, seventy-year-old men, in the base case scenario, the utility of pharmacotherapy is 18 QALY less than surgery, and the cost of pharmacotherapy is 136,301.1 $ less than surgery. ICER for pharmacotherapy was 7,572.3 $ compared to surgery. In the sensitivity analysis, the model is not sensitive to most variables but the unit cost of dutasteride. Based on scenario analysis conducted for different age groups, pharmacotherapy with dutasteride is preferred to surgery in patients over 60 years of age in Iran. However, for younger adult men between 40-60 years old, surgery is a cost-effective alternative.

Personal care products (PCPs) are generally used for personal hygiene, cleaning, grooming, and beautifcation. These include hair and skin care products, baby care products, UV  blocking creams, facial cleansers, insect repellents, perfumes, fragrances, soap, detergents, shampoos, conditioners, toothpaste, etc., thus exposing humans easily. Personal preferences related to PCPs usage frequency are highly variable and depend on socioeconomic status and lifestyle factors. The increasing availability and diversity of PCPs from the retailer outlets consequently result in higher loading of PCPs into wastewater systems and, therefore, the environment. These compounds persistently and continuously release biologically active and inactive ingredients in the atmosphere, biosphere, geosphere, and demonstrating adverse effects on human, wild, and marine life. Advanced techniques such as granular activated carbon fltration and algae-based system may help biotransformation and remove PCP contaminants from water with improved effciency. Additionally, harmony among PCPs related regulations of different countries may encourage standard checks to control their manufacturing, sale, and distribution across the borders to ensure consumers’ safety. Furthermore, all intended ingredients, their concentrations, and instructions for frequency of use as per age groups may be clearly labeled on packages of PCPs. In conclusion, the emerging environmental contaminants of PCPs and their association with the growing risks of negative effects on human health and globally on the environment emphasize the chemical-free simple lifestyle.

Overexpression of the EpCAM in epithelial-derived neoplasms makes this receptor a promising target in antibody-based therapy. Due to the lack of N-glycosylation, Escherichia coli (E. coli) seems to be the most appropriate choice for the expression of antibody fragments. However, developing a robust and cost-effective process that produces consistent therapeutic proteins from inclusion bodies is a major challenge. Undoubtedly, it can be circumvented by the soluble expression of these proteins. Utilization of numerous genetically modified hosts and optimization of cultivation conditions are two effective approaches widely used to overcome the insolubility problem. Due to the cytoplasmic expression of DsbC and the ability to the correct formation of disulfide bonds, the Shuffle™ T7 strain can be a suitable host for the soluble production of recombinant proteins. Here, Box-Behnken design (BBD)- Response surface methodology (RSM) modeling was employed to develop optimized culture conditions for 4D5MOC-B scFv fragment production in SHuffle™ T7 strain while solubility and production level were considered as responses. Although both responses were significantly influenced by post-induction temperature, cell density at induction time, and IPTG concentration, the temperature had the largest effect. The maximum experimental soluble protein obtained by adding 1 mM of IPTG into the M9 medium when the cell density reached 0.7 at 23 ᵒC was 693.56 µg/mL which was in good correlation with the predicted value of 720.742 µg/mL. Predictable total expression value was also experimentally verified. This strategy can be scaled-up for the production of large amounts of scFvs from SHuffle™ T7 E. coli to facilitate their potential applications as therapeutic and diagnostic agents.

The purpose of this study is to compare oral betamethasone pulse therapy, methotrexate therapy and a combination of the two for patients with Alopecia Areata (AA) as an autoimmune disorder. In this study, 36 patients with severe AA were selected and classified into three groups of 12: 1- Oral betamethasone therapy (3 mg, once a week) with placebo; 2- Oral methotrexate (15 mg, once a week) with placebo; and 3- A combination of methotrexate (15 mg, once a week) and betamethasone (3 mg, once a week). The Severity Alopecia Tool (SALT) was used to measure improvements in the lesions through photographs, and the patients also rated their condition on the Visual Analogue Scale (VAS). Assessments were performed, and the results were compared at baseline and then at intervals of three months for nine months. The demographics and SALT score were similar in the three groups (P > 0.05). All the groups showed improvements in SALT, VAS and photographic scores three months after beginning the treatment (P < 0.001). Betamethasone therapy (P = 0.006) and combination therapy (P < 0.001) provided greater SALT improvement than methotrexate, and combination therapy led to a greater improvement in VAS and photographic findings compared to the two other groups (P < 0.05).Oral steroid, methotrexate and combination pulse therapy were effective treatments for AA, while oral steroid pulse therapy and combination therapy were superior to methotrexate.

Cancer is one of the most important causes of death all around the world. Screening plants and their secondary metabolites as cytotoxic agents is one of the common methods for identifying new compounds used in chemotherapy and inhibition cancer process. Caesalpinia bonduc (L.) Roxb. from the Fabaceae family was used for improving wound, fever, tumor, hydrocele, hernia, smallpox, toothache, inflammation, and as astringent, anthelmintic, antidiabetic, and antimalarial agent in traditional medicine. A bioassay-guided study of this species led to the isolation of three flavonoids. At first, the cytotoxicity of methanol extract of aerial parts (leaves and stems), seeds, and legumes of this plant was tested against MCF-7 and PC-3 by MTT assay. The methanol extract of legumes showed better inhibitory activities (IC50 < 500 µg/mL). As a result, this extract was selected for fractionation. In the next step, the ethyl acetate (EtOAc) fraction was selected for phytochemical analysis based on the inhibitory activity (IC50 = 170 ± 0.9 µg/mL). In this way, total phenol content (625 ± 7.2 GAE/g extract) and antioxidant activity (IC50 = 6.1 ± 0.3 µg/mL) was compared by BHT (IC50 = 13.5 ± 0.7 µg/mL). Finally, three compounds including, quercetin-3-methyl ether (1), kaempferol (2), and kaempferol-3-O-α-L-rhamnopyranosyl-1→2)-β-D-xylopyranoside (3) were isolated from EtOAc fraction, and all isolated compounds were tested for their cytotoxicity and compound 1 showed better inhibitory activity than other two compounds. This study suggests that Caesalpinia bonduc could be considered for further investigations as a natural source of biological compounds.

The lack of transparency and predictability seems to remain one of the major complaints in the pharmaceutical pricing procedure in Iran, but there is not enough official evidence to support it. The main objective of this study was to identify influential variables officially or unofficially influencing the pharmaceuticals pricing in Iran and also clarifying the degree of importance of each variable from the viewpoints of two groups: the pricing Commission members (owners of pricing procedure) and other stakeholders in the pharmaceutical sector. Semi-structured interviews with experts were performed to extract the influential variables. A Likert scale questionnaire was designed based on extracted variables and used in above-mentioned two groups of experts. The validity and reliability of the questionnaire were assessed before use. About 68 influential variables were extracted which classified into eight categories or domains. Less than 50% of extracted influential variables on pharmaceutical pricing have been mentioned in Iran pricing regulations. There were statistically significant differences between the two group's viewpoints in terms of importance and effect of some variables on pricing procedure. Conflict of interest, lack of transparency and a sound framework were found as the main problems in Iran pharmaceutical pricing procedure and may lead to "case-by-case" decision making. As such, the output of the pricing commission is not transparent and predictable for its beneficiaries.

The aim of the current study was to investigate the preventive and curative effect of Atriplex halimus L. (Ah) extract against the kidney damages induced by Sodium benzoate (SB) in rats. Thirty male albino rats were divided into five groups of 6 rats each: Control, Ah, SB, AhP+SB and SB+AhC. SB (100 mg/kg b.w) was added to drinking water for 15 weeks. Aqueous extract of aerial parts of Atriplex halimus received intragastrically during the last 30 days of SB exposure for curative treatment (AhC) and all the duration of SB exposure for preventive treatment (AhP). Some Biochemical markers, oxidative stress parameters and histopathology of kidney tissue were studied. Administration of Sodium benzoate to rats caused a loss of weight and a significant elevation in creatinine, urea, renal malondialdehyde levels and lactate dehydrogenase activity. These changes were accompanied by decreasing in antioxidant defenses, like reduced glutathione level, catalase and glutathione S transferase activities in the kidney. Histopathological studies showed a massive degeneration in kidney tissue in SB-exposed rats. However, treatment with Atriplex halimus (A. halimus) restored the altered of biochemical and oxidative stress markers. A. halimus also regenerated the architectural kidneys lesions to near control. With more protection offered in the curative than preventive models of treatment. In conclusion, the results demonstrate that Sodium benzoate damages kidney structure and function and is a nephrotoxic substance. Atriplex halimus was able to improve the renal damage as an antioxidant and a nephroprotective agent.

The aim of this study was to develop and compare the pharmacokinetic property of testosterone undecanoate (TU) nano-/microcrystal suspension with three different particle sizes after intramuscular (i.m.) administration. TU nano-/microcrystal suspensions were prepared by high pressure homogenization method and the mean particle size was 0.30 ± 0.11 μm (A), 1.21 ± 0.37 μm (B), and 4.83 ± 0.60 μm (C), respectively. Scanning electron microscope (SEM) was employed to observe the morphology of nano-/microcrystal suspensions after operation. X-ray Powder diffraction (XRPD) confirmed the crystalline state of TU in nano-/microcrystal suspension. After storage at 4 °C and 25 °C under mechanical shaking for 2 months, physical and chemical stabilities of nano-/microcrystal suspensions were measured by particle size analyzer and high performance liquid chromatography. There was no obvious change in particle size distribution and content of TU. After i.m. administration of suspension C to rats, the concentration of TU in plasma lasted for nearly 12 days that was comparative with the commercial testosterone undecanoate injection. The results showed that microcrystal C with a larger particle size had long-acting effect comparing with other two suspensions. The muscle irritation test in rabbits showed that the local irritation of TU nano-/microcrystal suspensions was lower than that of commercial testosterone undecanoate injection. It can be concluded that appropriate particle size of nano-/microcrystal suspensions for i.m. administration of TU was important to achieve better therapeutic effect.

This study aimed to assess the additive value of olanzapine to a combination of ondansetron and dexamethasone to prevent chemotherapy-induced nausea and vomiting (CINV) in pediatric patients. A total of 40 patients between 4 to 18 years of age were enrolled in this randomized clinical trial. Both groups received a combination of ondansetron and dexamethasone, and 0.14 mg/kg olanzapine or matched placebo were administered for olanzapine and control groups, respectively. The primary end points were complete response and lack of nausea as far as three days after chemotherapy evaluated by the Common Terminology Criteria for Adverse Effects (CTCAE) v5.0 and the Multinational Association of Supportive Care in Cancer (MASCC) Anti-emesis Tool (MAT). Side effects of olanzapine were also analyzed. In patients receiving the standard regimen of ondansetron and dexamethasone, nausea was observed in 10.5% and 21% of patients according to MAT and CTCAE scales, respectively. In the olanzapine group, 37.5% (MAT scale) and 31.3% (CTCAE scale) of patients developed nausea. Complete response was observed in 84% (MAT scale) and 94.7% (CTCAE scale) of patients in the placebo group receiving ondansetron and dexamethasone. In comparison, it was observed in 87.5% (MAT scale) and 81.25% (CTCAE scale) for patients allocated to the olanzapine group. Neither acute nor delayed CINV was statistically different between placebo and olanzapine groups. The frequency of adverse effects was higher in the olanzapine group. Adding olanzapine to the standard regimen of CINV prophylaxis was only unhelpful in pediatric patients receiving moderately emetogenic chemotherapy but also associated with a higher rate of minor side effects.

The purpose of the current study was to prepare and characterize the targeted solid lipid nanoparticles(SLNs) containing docetaxel (DTX) for prostate cancer treatment. The goal has been achieved by locating anisamide (Anis) ligand on the surface of SLNs, which can interact with the overexpressed sigma receptor on the prostate cancer cells. DTX loaded SLNs were prepared by high shear homogenization and ultra-sonication method and optimized by applying experimental design. The average particle size and the entrapment efficiency of the optimum DTX-SLN were 174 ± 9.1 nm and 83 ± 3.34%, respectively. The results of differential scanning calorimetry showed that DTX had been dispersed as amorphous in the nanocarriers. Scanning electron microscopy (SEM) images confirmed the nanoscale size and spherical shape of the nanoparticles. The cytotoxicity studies have demonstrated that IC50 of free drug, DTX-SLN and DTX-SLN-Anis was 0.25 ± 0.01, 0.23 ± 0.02, 0.12 ± 0.01 nM on PC3 cell line and 20.9 ± 3.89, 18.74 ± 7.43, and 14.68 ± 5.70 nM on HEK293 cell line, respectively. Targeted DTX-SLN-Anis was acted more effectively on prostate cancer cells in comparison to DTX-SLN and free drug. The results of this study have depicted that the anti-cancer drug loaded in targeted SLNs can be a promising way for cancer treatment. In addition, performing in-vivo studies will be complementary to these findings.

Host modulation therapy is recently employed to improve periodontal treatments outcome. This randomized controlled clinical trial aimed to evaluate the effects of Semelil (ANGIPARS) as an adjunct to non-surgical treatment in patients with chronic periodontitis. Forty-four healthy subjects with moderate to severe chronic periodontitis were enrolled in the study. After completion of phase I periodontal therapy, including oral hygiene instruction, scaling, and root planing, the patients were randomly divided into two groups to receive capsules of Semelil (test) or placebo (control), consuming two capsules a day for three months. Clinical parameters (probing depth [PD], clinical attachment level [CAL], modified sulcular bleeding index [MSBI], modified gingival index [MGI], and plaque index [PI]) and biochemical parameters (interleukin-1β [IL-1β], 8-hydroxy-2-deoxyguanosine [8-OHdG]), and lipid peroxidation [LPO]) were measured at baseline and after completion of treatment. Twenty-five patients completed the study: 15 in the test group and 10 in the control group. All clinical and biochemical parameters were significantly improved from baseline to the final measurements in both groups (p < 0.001). The changes were more pronounced in the test group in comparison to the control group. However, the differences between the groups were significant only for MGI, MSBI, PD, and CAL (p < 0.05). Semelil may reveal promising results as an adjunctive treatment for chronic periodontitis.

While logical use of medicine is a priority in all health systems, people do self-medication- mainly using Nonprescription Drugs or Over the Counter (OTC) drugs- for different reasons. Self-medication is rising in many developing countries that could increase healthcare expenditure. The present study aimed to find the self-medication rate and predisposing, enabling, and need factors affecting it based on the Anderson behavioral model in the Iranian population. The present study uses 22470 households’ data acquired from Iranian utilization of healthcare survey at the national level (2016). Due to the study objective, the data of 13005 people who were over 15 years old and had outpatient healthcare needs two weeks before the survey. The survey included a binary question about self-medication, which is considered a dependent variable. Age, gender, marital status, literacy, job status, socio-economic status, location, basic health insurance, complementary health insurance, and need for health services were considered as independent variables. Data were analyzed using logistic regression. The self-medication rate was calculated at 26.3% that was different among different subgroups of the population. According to the model estimates, married (OR = 0.80, CI = 0.71-0.91) and housekeepers (OR = 0.79, CI = 0.67-0.93) had significantly lower self-medication. Moreover, the urban population (OR = 1.29, CI = 1.17-1.43), people without basic (OR = 1.32, CI = 1.10-1.58), and supplementary (OR = 1.18, CI = 1.04-1.35) health insurance and also people who had two or higher number of outpatient healthcare needs had significantly more self-medication (OR = 2.96, CI = 2.67-3.29). It can be concluded that need, enabling, and predisposing factors are respectively the main determinants of self-medication behavior. From a policy point of view, increasing effective health insurance coverage with a focus on people who have more health care needs can be helpful.

Neuropathic pain originates from illness or damage of the nervous system and affects the somatosensory system. Recently, many efforts have been made to illuminate the influences of neuropathic pain in different parts of central nervous system (CNS). However, the toxic consequences of neuropathic pain in glial cells, which involve in the control of pain is poorly understood. Therefore, the present study aimed to assess the molecular and cellular effects of neuropathic pain in the glial cells of rat brain. Induction of neuropathic pain in rats was associated with oxidative stress as evident by elevated reactive oxygen species (ROS) formation as well as reversible glutathione (GSH) depletion in the glial cells. Moreover, neuropathic pain caused mitochondrial membrane potential collapse (ΔΨm%), lysosomal membrane rapture, and proteolysis, probably due to ROS-induced MPT pore opening. These toxic events could cause cytochrome c release from intermembrane space into the cytosole and trigger caspase activation pathway. Our finding confirmed that the activity of caspase-3 was significantly increased in the glial cells as a core component of the apoptotic machinery. In conclusion, the neuropathic pain induces ROS generation as the major cause of GSH depletion along with mutual mitochondrial/lysosomal potentiation (cross-talk) of oxidative stress in the glial cells. Subsequently, this toxic cross-talk can induce proteolysis and trigger apoptosis by caspase-3 activation in the glial cells of rat brain.

Platinum-based drugs are the mainstay of chemotherapy regimens in a clinic, but their use is seriously limited by severe side effects and drug resistance. A cetuximab-decorated drug delivery system can selectively deliver drugs into EGFR-highexpressing cancer cells to prevent the shortcomings of platinum-based chemotherapy. Here, cetuximab-decorated and near-infrared (NIR)-activated nanoparticles based on Pt(IV)-prodrug (abbreviated as Cetuximab-Pt-INPs) was constructed. First, PEGylated Pt(IV)-prodrug was synthesized by a condensation reaction between c,c,t-[Pt(NH3)2Cl2(OOCCH2CH2COOH)(OH)] and MPEG-PLA. Then, Pt(IV)-prodrug and indocyanine green co-encapsulated nanoparticles (Pt-INPs) were prepared through an ultrasonic emulsification method. Finally, Cetuximab-Pt-INPs were obtained by decorating Pt-INPs with cetuximab as a targeting vector. The optimized Cetuximab-Pt-INPs exhibited a spherical coreshell shape of 138.5 ± 0.96 nm. In-vitro cellular uptake and cytotoxicity assays revealed that more Cetuximab-Pt-INPs with NIR irradiation were selectively taken up by A431 cells, thereby leading to higher cytotoxicity. These multifunctional nanoparticles may have promising potential for targeted and effective therapy against EGFR-highexpressing cells of epidermoid carcinoma.

In spite of successful initial remission, chemo-resistance and relapse are still concerning points in acute myeloid leukemia (AML) treatment strategies. Multidrug resistance (MDR) appears to be the major contributor of chemo-resistance, arising in some sub-clones of cancers and could be developed in others. The aim of this study was to investigate the role of extracellular vesicles (EVs) derived from AML patients on the transmission of chemo-resistance phenotype. Ultracentrifugation was employed to isolate EVs from healthy controls, new cases, and relapsed AML patients. The EVs size, morphology, and immunophenotype were determined by dynamic light scattering, TEM, and flow cytometry respectively. Bradford assay was performed to measure the protein content of EVs. MTT assay and flow cytometry analysis were also used to determine the viability index, induction of apoptosis, and ROS generation in U937 cells. The  expression level of two efflux pumps was assessed using qRT-PCR analysis. Findings of TEM, DLS, and flow cytometry confirmed that EVs had a desirable shape, size, and surface markers. EVs derived from both new cases and relapsed AML patients significantly reduced idarubicininduced apoptosis in the U937 cells. The analysis of drug efflux pumps gens revealed that EVs over-express MRD1 and MRP1 in the target cells. These findings suggested a novel role of EVs in mediating the acquired chemo-resistance in AML patients by inducing the expression of the drug efflux pumps; however, further investigations will be required to elucidate other underlying mechanisms of resistance that are mediated by EVs.

The aim of this study was to evaluate the expression Nrf2 (Nuclear factor-erythroid 2-p45 derived factor 2) and Keap1 (Kelch-like ECH-associated protein 1) genes and Bcl-2 (B-cell lymphoma 2), Bcl-XL (B-cell lymphoma-extra large), Bax (Bcl2-associated X protein) apoptotic pathway genes in acute myeloid leukemia patients. In this case-control study, the expression of genes encoding Nrf2, Keap1, Bcl2, Bcl- XL and Bax in 40 acute myeloid leukemia (AML) patients were compared with 40 normal individuals in the Iranian population. We evaluated the mRNA expression of genes by using the real-time quantitative polymerase chain reaction. The expression of Nrf2, Bcl2 and Bcl- XL genes in new AML patients were increased (p < 0.05). The patients treated with chemotherapy had a significantly more than four times higher expression level of Nrf2 than new case patients (P < 0.05), while there was a decrease in the expression level of Bcl2 and Bcl-XL, which was not statistically significant. In other hands in relapsed patients, the expressions of Nrf2, Bcl2 and Bcl- XL were higher level than new case patients (p < 0.05) but this was less than patients treated with chemotherapy (p > 0.05). The high levels of mentioned genes may be associated with poor treatment response, chemoresistance and disease recurrence. Because of hyperactivation and overexpression of Nrf2 in leukemia, suggest that Nrf2 inhibitors could be used as a pharmacological target in combination with classical chemotherapeutic agents to increase the efficacy of anticancer therapy.

Acquired immunodeficiency syndrome (AIDS) is still an incurable disease with increasing mortality rate. Despite the development of effective FDA-approved anti-HIV drugs, there are some problems due to the growing of resistant viral strands. Therefore, discovery of novel anti-HIV agents is so needed. Integrase, targeted in highly active antiretroviral therapy (HAART), is a crucial enzyme in viral replication. In this study, new benzimidazolyl diketo acid derivatives were designed according to required features for inhibitors of HIV-1 integrase. Designed compounds were synthesized and evaluated for anti-HIV-1 effects. According to the cell-based biological assay’s results, most of the tested compounds demonstrated good anti-HIV-1 activity, ranging from 40-90 µM concentration with no severe cytotoxicity. The most potent compound was 13g with EC50 value of 40 µM and CC50 value of 550 µM. Docking analysis of compound 13g in integrase active site was in good agreement with well-known integrase inhibitors, proposing that anti-HIV-1 potency of compounds may be via integrase inhibition.

Previous studies have shown that alcohol abuse can cause serious liver damage and cirrhosis. The main pathway for these types of hepatocellular cell neurodegeneration is mitochondrial dysfunction, which causes lipid peroxidation and dysfunction of the glutathione ring and the defect of antioxidant enzymes in alcoholic hepatic cells. Alcohol can also initiate malicious inflammatory pathways and trigger the initiation and activation of intestinal and extrinsic apoptosis pathways in hepatocellular tissues that lead to cirrhosis. Previous studies have shown that curcumin may inhibit lipid peroxidation, glutathione dysfunction and restore antioxidant enzymes. Curcumin also modulates inflammation and the production of alcohol-induced biomarkers. Curcumin has been shown to play a critical role in the survival of alcoholic hepatocellular tissue. It has been shown that curcumin can induce and trigger mitochondrial biogenesis and, by this mechanism, prevent the occurrence of both intrinsic and extrinsic apoptosis pathways in liver cells that have been impaired by alcohol. According to this mechanism, curcumin may protect hepatocellular tissue from alcohol-induced cell degeneration and may therefore survive alcoholic hepatocellular tissue. . Based on these mechanisms, the protective functions of curcumin against alcohol-induced cell degeneration due to oxidative stress, inflammation, and apoptosis events in hepatocellular tissue have been recorded. Hence, in this research, we have attempted to evaluate and analyze the main contribution mechanism of curcumin cell defense properties against alcohol-induced hepatocellular damage, according to previous experimental and clinical studies, and in this way we report findings from major studies.